Anu Goenka,1 Benedict D. Michael,1 Elizabeth Ledger,2 Ian J. Hart,3 Michael Absoud,4 Gabriel Chow,5 James Lilleker,6 Michael Lunn,7 David McKee,8 Deirdre Peake,9 Karen Pysden,10 Mark Roberts,6 Enitan D. Carrol,1 Ming Lim,4 Shivaram Avula,11 Tom Solomon,1 and Rachel Kneen1 Clinical Infectious Diseases 2014;58(6):775–84(15 March) R3 박재훈 / Prof. 이미숙

 Neurological manifestations of influenza infection ◦ febrile seizures & encephalopathy(m/c) in children(3/4) ◦ In Japan, influenza : m/c pathogen in acute encephalopathy ◦ In US & Australia, 6%–19% of children hospitalized with influenza infection have neurological manifestations  “influenza-related encephalopathy” has been subclassified into a range of specific acute encephalopathy syndromes(AESs) ◦ acute necrotizing encephalopathy (ANE) ◦ acute hemorrhagic leukoencephalopathy (AHL)  inherited mutations in the Ran-binding protein 2 (RANBP2) gene

 A multicenter surveillance study of children & adults through British Pediatric Neurology Association(BPNA) & the Association of British Neurologists (ABN) between ~  Cases with an acute neurological presentation occurring within 1 month of proven influenza infection were included and were defined as positive PCR for influenza RNA from throat or nasal swab, respiratory secretions, serum, or CSF  Children : <18 years

25 cases (21 : children) from BPNA & ABN members Children(21) : median 4yrs 12 encephalopathy 8 encephalitis 1 meningoencephalitis Adult(4) : median 42yrs 2 encephalopathy 1 encephalitis 1 GBS All had fever or respiratory Sx. 12 seizures 3 circulatory shock 3 movement disorder 2 acute Parkinsonism

17 CSF exam 3 pleocytosis 12 EEG none epilepticform activity 20, med 3days rd cepha 9 acyclovir Glasgow Outcome Scale 8 good 13 poor (4 very poor)

 1-year-old white boy  2-day coryzal illness  floppy, with respiratory distress, circulatory shock, decorticate posturing  ALT : 1319 IU/L  CXR : patchy changes bilaterally / Brain CT : normal  ICU and antimicrobial Tx(cefotaxime, clarithromycin, acyclovir, oseltamivir)  Brain MRI(day 10) : cerebral atrophy, bilateral symmetrical restricted diffusion involving the frontal cortex  sequelae: tracheostomy, at 6 months he was unable to sit, Bulbar function was abnormal, and he required a percutaneous gastrostomy

 A previously well 2-year-old white boy  2-day history of pyrexia, diarrhea, vomiting  GCS dropped to 4/15 over several hours & signs of raised ICP  ventilator & iv mannitol, ceftriaxone, acyclovir, oseltamivir  Brain CT : edema of thalami, basal ganglia, brainstem  ARF & liver failure (ALT IU/L) c coagulopathy  Brain MRI (day 5) : multiple symmetrical thalamic lesions  He died despite despite with MPD & IVIG  Investigations to look for underlying metabolic, genetic, and autoimmune causes were negative

 3-year-old girl of South Asian ethnicity  2-day coryzal illness & brief generalized tonic-clonic seizure  drowsy with refractory circulatory shock  Initial antimicrobial Tx(ceftriaxone, acyclovir)  During intubation  bradycardic  CPR  ARF & hepatic failure(ALT 3192 IU/L), coagulopathy, hypernatremia, lactic acidosis  Brain CT : diffuse cerebral edema  Antimicrobial Tx(cefotaxime, clarithromycin, oseltamivir, acyclovir)  12 hrs after presentation  brainstem death and bilateral retinal hemorrhages

 42-year-old white woman with well-controlled asthma  1-day history of Lt. pleuritic chest pain, dyspnea, pyrexia  Antibiotics(amoxiclav & clarithromycin + piperacillin/tazobactam, oseltamivir)   vasopressors & invasive ventilation  Blood cx : S. pneumoniae (antibiotics  iv benzylpenicillin)  Brain CT : significant cerebral edema  EEG : severe encephalopathy   mannitol & ventilator  f/u brain CT(3days after) : worsening cerebral edema   lost brain stem reflexes  Postmortem examination : AHL

 This surveillance study described a cohort of adults and children with neurological manifestations of influenza, many with poor outcomes  None of the patients had been vaccinated despite indications, and therefore their deaths or poor outcome may have been prevented  A broad spectrum of acute encephalopathy syndromes was identified, frequently associated with poor outcomes  These data are used to propose a new classification of influenza-related neurological manifestations